BACKGROUND: The HEmochromatosis and IRon Overload Screening
(HEIRS) Study provided data on a racially, ethnically and geographically
diverse cohort of participants in North America screened from primary
care populations.METHODS: A total of 101,168 participants were screened by testing for
HFE C282Y and H63D mutations, and measuring serum ferritin concentration
and transferrin saturation. In the present review, lessons from the
HEIRS Study are highlighted in the context of the principles of screening
for a medical disease as previously outlined by the World Health
Organization.RESULTS: Genetic testing is well accepted, with minimal risk of discrimination.
Transferrin saturation has high biological variability and relatively
low sensitivity to detect HFE C282Y homozygotes, which limits its role as a
screening test. Symptoms attributable to HFE C282Y homozygosity are no
more common in individuals identified by population screening than in
control subjects.CONCLUSIONS: Generalized population screening in a primary care
population as performed in the HEIRS Study is not recommended. There
may be a role for focused screening in Caucasian men, with some debate
regarding genotyping followed by phenotyping, or phenotyping followed by
genotyping.